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Understanding Axonal Outgrowth and Cell Movement

A look into the mechanisms of axonal growth and cell movement.

― 6 min read


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Axonal outgrowth is the process by which neurons extend their axons to connect with other neurons. This process is critical for the development and functioning of the nervous system. It involves various mechanisms that help transport proteins and other materials necessary for growth. The movement of a structure called the growth cone at the tip of the axon is essential in this process. The growth cone moves forward, helping to establish connections between neurons.

Mechanisms Behind Axonal Growth

The transport of materials supporting axonal outgrowth occurs through different methods. These include the movement of organelles, the slow transport of proteins, and the flow of the cellular structure made up of proteins called cytoskeletal elements. The proteins needed for axonal growth are predominantly produced in the neuron’s cell body and then transported down the axon.

Research shows that there are similarities between how cells move during other processes, such as cell division and cell crawling. This has led scientists to make connections between these distinct types of movement. However, the detailed relationships between these types of movement are not fully understood.

Cell Movement and the Flow of Cytoskeleton

Cell movement relies on the flow of cytoskeletal elements. These are networked structures made up of proteins that provide support and shape to the cell. They allow the cell to move and change form. This flow is influenced by molecular motors and adhesion molecules, which help the cell stick to surfaces. Various forms of movement, such as cell division and different types of migration, share common features in terms of how the cytoskeleton flows and how cells interact with their surroundings.

In migrating cells, specific areas called convergence zones have high activity, helping to pull the cell forward. As cells crawl or move, they generate forces that allow them to grip onto surfaces and move in a specific direction. This process of adhesion is crucial as it helps the cell maintain stability as it moves.

Growth Cones and Their Function

Growth cones behave similarly to migrating cells. In neurons, the region known as the lamellipodium at the front of the growth cone is essential for movement. It shows retrograde flow, meaning that the internal structure moves backward while new materials continuously flow forward. This helps create the necessary forces for the growth cone to advance.

The central part of the growth cone, known as the central domain, is rich in organelles and microtubules, which are important components of the cytoskeleton. As the growth cone moves forward, the materials in the axon also flow toward the tip. This helps in sustaining the growth of the axon.

Discovering Links Between Different Types of Cell Movement

It is known that during the process of cell division, the elements that help the cell pull apart also have roles in aiding cell crawling. There are proteins that assist in both processes, and the mechanisms that allow for movement are quite similar. The RhoA pathway, which regulates certain motor activities, is involved in cell division, crawling, and axon growth.

Researchers have been trying to connect the findings from various types of cell movement using a single model. By examining the forces at play and how they vary, scientists aim to identify a common understanding of how these movements occur.

Developing a Fluid Model for Cell Movement

To study the movements of cells, especially during axonal outgrowth and migration, scientists have proposed an active fluid model. This model represents how the cytoskeleton flows and how forces are generated. In a simplified view, cells can be thought of as collections of filaments that can act like solids or fluids, depending on the time frame considered.

When looking at short timeframes, cells behave solidly, but over longer periods, the structure flows like a liquid. This flexibility allows researchers to predict how cells move based on the interactions of their components.

The Role of Adhesion in Cell Motion

A key concept in understanding how cells move is the idea of adhesion. When adhesion is strong, it can stop or slow down cell movement. Conversely, when adhesion is weak, cells can flow more freely. This balance is crucial as it shapes how cells crawl, divide, and grow.

For instance, in migrating cells, adhesion under the front part of the cell can drive motion forward. In contrast, weak adhesion at the back allows the trailing edge to move more freely. This difference is essential in directing the cell's overall movement and behavior.

Comparison of Various Types of Cell Motility

Cells involved in cytokinesis, amoeboid migration, and mesenchymal migration exhibit similar flow patterns, even though they may look different. During cytokinesis, cells have a bilobate shape, with a clear zone of activity pulling components inward. In amoeboid migration, the shape may vary, but the inward flow pattern remains. Mesenchymal cells also show similar patterns, focusing on strong cell-substrate Adhesions that guide movement.

Different types of cells have also been observed, and their movements can be accounted for using similar models. For instance, while migrating neurons have distinct physical features, their movement still parallels those of other cell types under certain conditions.

Neuronal Migration and Axon Outgrowth

When it comes to neuron behavior, there are notable similarities between neuronal migration and axon outgrowth. During neuronal migration, materials move forward, and the growth cone behaves similarly. However, during axonal outgrowth, the materials in the proximal axon relative to the cell body are stationary, contrasting the constant motion seen in migrating neurons.

The model predicts that this shift in behavior is linked to different adhesion strengths under the axon, influencing how the axon extends and how the cells manage their movement.

Observations About Cell Movement

In summary, there are a number of shared qualities and mechanisms between various forms of cell movement. The understanding gained through studying axon growth can also shed light on how cells crawl and divide. Adhesion strength, flow patterns, and contractile zones all play significant roles in these processes.

Experimental Approaches to Study Movement

To better understand these dynamics, researchers have utilized techniques such as time-lapse imaging to visualize movements and gather data. By comparing the findings across different types of cells and conditions, scientists can identify general principles that govern cell behavior.

Future research will likely involve more complex models that can account for the subtleties of each motion type. By measuring the physical parameters governing each process, scientists aim to develop a more unified understanding of how these diverse forms of movement relate to one another.

Conclusion

Ultimately, the goal is to develop a comprehensive model that connects the processes of cell division, migration, and axon outgrowth. By recognizing the similarities in these mechanisms and the roles of adhesion and force generation, researchers can formulate predictions about how cells interact with their environments and advance their growth.

As knowledge continues to accumulate, it will become increasingly possible to apply this understanding across various fields, potentially leading to advancements in medical science and biotechnology. Understanding axonal outgrowth and related processes may help in devising treatments for conditions affecting the nervous system and could pave the way for innovations that enhance tissue repair and regeneration.

Original Source

Title: A simple active fluid model unites cytokinesis, cell crawling, and axonal outgrowth

Abstract: Axonal outgrowth, cell crawling, and cytokinesis utilize actomyosin, microtubule-based motors, cytoskeletal dynamics, and substrate adhesions to produce traction forces and bulk cellular motion. While it has long been appreciated that growth cones resemble crawling cells and that the mechanisms that drive cytokinesis help power cell crawling, they are typically viewed as unique processes. To better understand the relationship between these modes of motility, here, we developed a unified active fluid model of cytokinesis, amoeboid migration, mesenchymal migration, neuronal migration, and axonal outgrowth in terms of cytoskeletal flow, adhesions, viscosity, and force generation. Using numerical modeling, we fit subcellular velocity profiles of the motions of cytoskeletal structures and docked organelles from previously published studies to infer underlying patterns of force generation and adhesion. Our results indicate that, during cytokinesis, there is a primary converge zone at the cleavage furrow that drives flow towards it; adhesions are symmetric across the cell, and as a result, cells are stationary. In mesenchymal, amoeboid, and neuronal migration, the site of the converge zone shifts, and differences in adhesion between the front and back of the cell drive crawling. During neuronal migration and axonal outgrowth, the primary convergence zone lies within the growth cone, which drives actin retrograde flow in the P-domain and bulk anterograde flow of the axonal shaft. They differ in that during neuronal migration, the cell body is weakly attached to the substrate and thus moves forward at the same velocity as the axon. In contrast, during axonal outgrowth, the cell body strongly adheres to the substrate and remains stationary, resulting in a decrease in flow velocity away from the growth cone. The simplicity with which cytokinesis, cell crawling, and axonal outgrowth can be modeled by varying coefficients in a simple model suggests a deep connection between them.

Authors: Kyle Edward Miller, E. M. Craig, F. Oprea, S. Alam, A. Grodsky

Last Update: 2024-05-23 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.05.22.595337

Source PDF: https://www.biorxiv.org/content/10.1101/2024.05.22.595337.full.pdf

Licence: https://creativecommons.org/licenses/by/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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